Pathogenetic difference between collagen arthritis and adjuvant arthritis.

Abstract

Collagen arthritis can be induced readily in many strains of rats by immunizing them with heterologous or homologous native type II collagen emulsified in incomplete Freund's adjuvant (1). This disease, which is characterized by the development of both cellular and humoral immune response to type II collagen (2-4), can be passively transferred by sensitized spleen and lymph node cells (5) as well as IgG antibodies to type II collagen (6). These findings are consistent with the proposal that collagen arthritis is the result of immunologic hypersensitivity to type II collagen. In a recent report, Trentham et al. (7) showed that rats with adjuvant arthritis exhibited both humoral and cellular sensitivities to homologous type II collagen, and suggested that an autoimmune response to type I! collagen is a common feature to both collagen arthritis and adjuvant arthritis. However, subsequent studies (8, 9) have produced conflicting results that shed some doubt on this exciting concept, and the discrepancies need further clarification.The present study was intended to determine if an autoimmune response to type II collagen is responsible for the induction of both collagen arthritis and adjuvant arthritis by using a relatively new immunosuppressive agent, cyclosporin, which has been shown to be capable of inducing specific immunologic tolerance in several in vivo and in vitro conditions (10, 1 I). Materials and MethodsAnimals. Outbred female Sprague-Dawley rats were purchased from Japan Charles River Breeding Laboratories, Kanagawa, Japan. They were allowed 1 wk to adapt to their environment and were used at 6 wk old, weighing 130-160 g at the start of the present experiment. All the animals received standard laboratory chow and water ad libitum. Preparation of Type II Collagen and Production of Collagen Arthritis.Type II collagen was isolated and purified from bovine articular cartilage as previously described (1). The purity was assessed as described elsewhere (12). Lyophilized type II collagen was dissolved in 0.I M acetic acid at a concentration of 3 mg/ml. Equal volumes of collagen solution and incomplete Freund's adjuvant (Difco Laboratories, Inc., Detroit, MI) were emulsified using a homogenizer (Polytron PT 10-35; Kinematica, Lucerne, Switzerland) and kept cold with an ice bath. Collagen arthritis was produced by intradermal injection of 1 ml of Address correspondence to N. Kaibara,

Regulation of resistance against adjuvant arthritis in the Fisher rat

“…Furthermore, timing of administration is also of importance, since 20 mg/kg Cy given on days 0-2 after adjuvant prevented the development of arthritis in Sprague-Dawley rats [29]. There Unfortunately CsA treatment at later time points, to eliminate these up-regulated T suppressor cells, is of limited use, since it has been frequently shown that this results in a suppression in several arthritis models [30][31][32][33].…”

Inhibition by cyclosporin A of streptococcal cell wall‐induced arthritis and hepatic granulomas in rats

“…Cyclosporin A (CsA), a new immunoregulatory drug, has recently been studied in several animal models of arthritis and chronic inflammation (1)(2)(3)(4)(5). In the type I1 collagen model of arthritis in rats, continuous daily administration of CsA has been shown to reduce both joint swelling and titers of antibody to type I1 collagen when CsA was started prior to introduction of antigen (1)(2)(3).…”

“…In the type I1 collagen model of arthritis in rats, continuous daily administration of CsA has been shown to reduce both joint swelling and titers of antibody to type I1 collagen when CsA was started prior to introduction of antigen (1)(2)(3). However, if given after antigen administration, CsA enhances both joint swelling and type I1 collagen-antibody titers (1).…”

Inhibition by FK506 of established lesions of collagen-induced arthritis in rats

“…The lesions of the four paws were each graded from 0 to 4 according to the increasing extent of periarticular erythema and swelling as well as joint deformity, as described previously (Kaibara et al, 1983 (Kaibara et al, 1983), adapted from the method of Voller, Bidwell & Bartlett (1976). The quantity of IgG antitype II collagen antibody was expressed as milligrams per 100 ml serum by comparison with standard curves obtained from an affinity-purified rat antitype II collagen antibody control (Kaibara et al, 1984).…”